Late yesterday afternoon, Matthew Herper broke the news that Juno Therapeutics had had their CAR-T leukemia trial put on hold after three patient deaths. That’s bad news no matter how you look at it, even for their competitors.
It’s too early to say for sure if Juno will be slowed in its path to market. In an interview, Bishop and Juno chief financial officer Steven Harr said that they think they understand why the deaths occurred, that they think they can get the trial back on track quickly, and that they do not think this will affect the development of the other 8 CART programs the company is pursuing.
Bishop says that the culprit appears to be a new drug, the chemotherapy fludarabine, that Juno recently added to the trial, called ROCKET. In the CART treatment, patients are first given a chemo cocktail that kills their existing T-cells. This gives the new T-cell, genetically re-engineered to attack cancer, room to grow. Juno has previously presented work showing that adding a drug called fludarabine to the chemotherapy makes the CART cells take root faster. For this reason, JUNO decided to start adding fludarabine to patients partway through.
As that second link above (from Adam Feuerstein) says, though, later in the evening Juno said that they’re going to be delayed for at least a year. The deaths were due to cerebral edema, and if that’s due to the fludarabine treatment, well, others in this field are apparently using it as well. Herper’s article says that the three deaths seem to be out of fewer than ten patients who have seen this combination thus far, so that’s very, very bad indeed. Since we’re dealing with the immune system, though, the potential for very specific, very dramatic effects (both good and bad) is always there, and it may be that Juno’s particular CAR-T approach interacts particularly badly.
But we don’t know that yet. And until we do know something, the whole field is going to be moving cautiously. Or so you’d think – as Feuerstein notes, Kite Therapeutics took the opportunity last night to issue a press release about how they themselves had completed enrollment in their latest CAR-T trial. Classy. They need to go read up on hubris and Nemesis and consider reining it in a bit, because guess what? They don’t know what’s going to happen next, either. No one does. A little humility might be appropriate when dealing with therapies that we don’t completely understand and which can either pull patients practically out of the grave or kill them without warning.
Update: the FDA lifted the clinical hold after about three days, so onward we go . . .